981 research outputs found

    Joint modeling of ChIP-seq data via a Markov random field model

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    Chromatin ImmunoPrecipitation-sequencing (ChIP-seq) experiments have now become routine in biology for the detection of protein-binding sites. In this paper, we present a Markov random field model for the joint analysis of multiple ChIP-seq experiments. The proposed model naturally accounts for spatial dependencies in the data, by assuming first-order Markov dependence and, for the large proportion of zero counts, by using zero-inflated mixture distributions. In contrast to all other available implementations, the model allows for the joint modeling of multiple experiments, by incorporating key aspects of the experimental design. In particular, the model uses the information about replicates and about the different antibodies used in the experiments. An extensive simulation study shows a lower false non-discovery rate for the proposed method, compared with existing methods, at the same false discovery rate. Finally, we present an analysis on real data for the detection of histone modifications of two chromatin modifiers from eight ChIP-seq experiments, including technical replicates with different IP efficiencies

    CORE_TF: a user-friendly interface to identify evolutionary conserved transcription factor binding sites in sets of co-regulated genes

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    <p>Abstract</p> <p>Background</p> <p>The identification of transcription factor binding sites is difficult since they are only a small number of nucleotides in size, resulting in large numbers of false positives and false negatives in current approaches. Computational methods to reduce false positives are to look for over-representation of transcription factor binding sites in a set of similarly regulated promoters or to look for conservation in orthologous promoter alignments.</p> <p>Results</p> <p>We have developed a novel tool, "CORE_TF" (Conserved and Over-REpresented Transcription Factor binding sites) that identifies common transcription factor binding sites in promoters of co-regulated genes. To improve upon existing binding site predictions, the tool searches for position weight matrices from the TRANSFAC<sup><it>R </it></sup>database that are over-represented in an experimental set compared to a random set of promoters and identifies cross-species conservation of the predicted transcription factor binding sites. The algorithm has been evaluated with expression and chromatin-immunoprecipitation on microarray data. We also implement and demonstrate the importance of matching the random set of promoters to the experimental promoters by GC content, which is a unique feature of our tool.</p> <p>Conclusion</p> <p>The program CORE_TF is accessible in a user friendly web interface at <url>http://www.LGTC.nl/CORE_TF</url>. It provides a table of over-represented transcription factor binding sites in the users input genes' promoters and a graphical view of evolutionary conserved transcription factor binding sites. In our test data sets it successfully predicts target transcription factors and their binding sites.</p

    Identifying a gene expression signature of cluster headache in blood.

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    Cluster headache is a relatively rare headache disorder, typically characterized by multiple daily, short-lasting attacks of excruciating, unilateral (peri-)orbital or temporal pain associated with autonomic symptoms and restlessness. To better understand the pathophysiology of cluster headache, we used RNA sequencing to identify differentially expressed genes and pathways in whole blood of patients with episodic (n = 19) or chronic (n = 20) cluster headache in comparison with headache-free controls (n = 20). Gene expression data were analysed by gene and by module of co-expressed genes with particular attention to previously implicated disease pathways including hypocretin dysregulation. Only moderate gene expression differences were identified and no associations were found with previously reported pathogenic mechanisms. At the level of functional gene sets, associations were observed for genes involved in several brain-related mechanisms such as GABA receptor function and voltage-gated channels. In addition, genes and modules of co-expressed genes showed a role for intracellular signalling cascades, mitochondria and inflammation. Although larger study samples may be required to identify the full range of involved pathways, these results indicate a role for mitochondria, intracellular signalling and inflammation in cluster headach

    Coupling of the lattice and superlattice deformations and hysteresis in thermal expansion for the quasi one-dimensional conductor TaS3_3

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    An original interferometer-based setup for measurements of length of needle-like samples is developed, and thermal expansion of o-TaS3_3 crystals is studied. Below the Peierls transition the temperature hysteresis of length LL is observed, the width of the hysteresis loop δL/L\delta L/L being up to 5⋅10−55 \cdot 10^{-5}. The behavior of the loop is anomalous: the length changes so that it is in front of its equilibrium value. The hysteresis loop couples with that of conductivity. The sign and the value of the length hysteresis are consistent with the strain dependence of the charge-density waves (CDW) wave vector. With lowering temperature down to 100 K the CDW elastic modulus grows achieving a value comparable with the lattice Young modulus. Our results could be helpful in consideration of different systems with intrinsic superstructures.Comment: 4 pages, 3 figures. Phys. Rev. Lett., accepted for publicatio
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